Prevalence of elevated blood lead levels in an inner-city pediatric clinic population.

In November 1997, the Centers for Disease Control and Prevention (CDC) released revised guidelines for lead poisoning screening, including a recommendation that states and regions individualize screening policies based on local prevalence of elevated lead levels. The purpose of this study was to collect prevalence data for a Philadelphia, Pennsylvania, inner-city pediatric outpatient population previously not known to have elevated blood lead levels in order to determine its risk for lead exposure and screening requirements. Charts were reviewed for 817 children of 10 months through 6 years of age whose venous blood lead levels were obtained as part of their routine health care over a 12-month period ending October 1992. None of these children had a history of previously elevated lead levels. Prevalence of elevated lead levels was determined for this population and correlated with patient age, sex, race, and insurance type. More than two-thirds (68%) of the study patients had a blood lead level of [Greater than and equal to]10 microg/dl. Elevated blood lead levels were associated with black race (p<0.0001), but not with sex or insurance type. The percentage of children with elevated blood lead levels was highest at ages 37-48 months. A majority of the children screened had lead levels in excess of the CDC threshold for an abnormal lead level (10 microgram/dl). This is the highest reported prevalence within a U.S. pediatric clinic population. In view of this extremely high prevalence, clinicians and public health personnel caring for children in Philadelphia inner-city clinics must follow the intent of the new CDC guidelines by increasing their efforts in the areas of screening, follow-up, and environmental interventions. To ensure a lead-safe upbringing for children in the United States, state health officials nationwide should perform local risk assessments before considering policy transitions from universal to targeted screening. ImagesFigure 1

It has recently been shown (Desgranges et al., 1986) that bromovinyluracil [BVU: (E)-5-(2-bromovinyl)uracil] increases the antitumour effect of 5fluorouracil (5-FU) in DBA/2 mice inoculated with P388 leukaemia cells, most likely by inhibiting 5-FU degradation in vivo. The inhibitory effect is apparently due to the effect of BVU on dihydrothymine dehydrogenase, the rate-limiting enzyme in the catabolism of pyrimidines. It has also been reported that bromovinyldeoxyuridine [BVDU; (E)-5-(2-bromovinyl)-2'-deoxyuridine] is rapidly converted to BVU in vivo (Desgranges et al., 1984) and induces the same synergistic antitumour effect with 5-FU as observed upon injection of BVU (Desgranges et al., 1986). BVDU itself is an antiviral compound with great promise for the treatment of herpes simplex virus (type 1) and varicella-zoster virus infections (de Clercq & Walker, 1984).
We have shown (Ben-Efraim et al., 1986) that treatment of MOPC-315 plasmacytoma tumour cells for 1 h with a minimal dose of 0. Ipg 5-FU/107 cells caused marked reduction in incorporation of (methyl)3H thymidine (up to 68% of the degree of thymidine incorporation in control untreated cells). No attempts were made to determine the effect of extending the length of the 5-FU treatment interval on tumour cells. In view of results obtained with other tumour lines (Drewinko & Yang, 1985), it might be that extending the length of 5-FU treatment of tumour cells will result in more marked inhibition of thymidine incorporation and possibly in reduction of the minimal effective dose of 5-FU.
The data indicating tumouricidal effect in vitro of 5-FU on MOPC-315 tumour cells prompted us to evaluate the effect of 5-FU therapy in mice bearing MOPC-3 15 plasmacytoma tumours. We found Correspondence: S. Ben-Efraim. Received 21 April 1986; and in revised form, 2 July 1986. (Ben-Efraim et al., 1986) that a single injection of 5-FU at 200mg kg-1 in BALB/c mice bearing large MOPC-3 15 plasmacytomas induced transient regression of the tumours. At doses <200mg kg-1, 5-FU was without effect (Ben-Efraim et al., 1986). In view of the inhibitory effect of BVDU (via BVU) on the degradation of 5-FU (Desgranges et al., 1986), it appeared of interest to determine whether low doses of 5-FU which did not affect development of established MQPC-315 plasmacytoma tumours alone, could be more effective when administered in combination with BVDU.
The MOPC-315 myeloma cell line employed in this study grows preferentially in the mouse BALB/c strain and is characterized by its ability to secrete anti-TNP trinitrophenyl) IgAA2 immunoglobulin (Eisen et al., 1968). Subcutaneous inoculation of 1 x 105 MOPC-315 tumour cells invariably induces formation of local tumour which reach a size of 15.0 mm on the 11th day after inoculation and death within 20 days. An in vitro line of MOPC-315 tumour cells, adapted to growth in culture (Yaniv et al., 1978), was maintained in RPMI 1640 medium (GIBCO, NY, USA), supplemented with 100 U ml-1 penicillin, 100 igml-1 streptomycin, 2 mmol ml-1 L-glutamine, and 10% foetal calf serum. The MOPC-315 cell line was used for evaluating the in vitro effects of BVDU and 5-FU on (methyl)3H thymidine (Nuclear Research Centre, Negev, Israel; 1.0 pCi/50 Ml/culture) incorporation in tumour cells. BVDU was synthesized at the Rega Institute for Medical Research Leuven, Belgium following a described procedure (Jones et al., 1979). 5-FU was kindly donated by Abic, Ramat-Gan, Israel. The effect of BVDU and 5-FU on MOPC-315 tumour cells in vitro were monitored in incubating 1 x 107 cells with varying compound concentrations for 1 h at 37°C, washing the cells with serum-free medium and further incubating the cell cultures as described (Bocian et al., 1984). For the experiments in vivo, groups of ten BALB/c mice ©) The Macmillan Press Ltd., 1986 H (8-12 weeks old) were inoculated s.c. with 1 x 105 viable MOPC-315 tumour cells. BVDU (200 jmol -69.5mgkg-1) was injected i.p. in a volume of 0.5ml on the 11th day after tumour cell inoculation, followed 1 h later by a single i.p. injection of varying doses of 5-FU in 0.5 ml. Untreated inoculated mice and mice treated with either BVDU or 5-FU alone served as controls. The mice were observed for 60 days for tumour development and death.
The significance of differences between groups treated with 5-FU alone and corresponding groups treated with 5-FU plus BVDU was calculated by the double tailed Mann-Whitney U test. The rate of tumour development in various groups as indicated by measurements of tumour sizes was compared till the 19th day after inoculation. Until this day, all of the inoculated mice were still alive in the compared groups. Differences were considered significant when P < 0.05. The therapeutic index (TI) was calculated as ratio of maximum tolerated dose (MLD) to minimum effective dose (MED). According to our previously reported data (Ben-Efraim et al., 1986) the MLD for 5-FU was 250mgkg-1 body weight. The MED was taken as the lowest quantity of 5-FU which induced significant transient regression of large MOPC-315 tumours. Injection of 5-FU, 100mg kg-1 body wt plus BVDU (69.5mgkg-1) in normal, noninoculated mice did not affect the survival of animals and did not cause appreciable loss of weight.
Exposure of MOPC-315 tumour cells in vitro to different concentrations of BVDU (0.5 to 100 Mg I10 cells) for h did not affect the rate of thymidine incorporation into the tumour cells. In keeping with previous results (Ben-Efraim et al., 1986), treatment of MOPC-315 tumour cells with 5-FU markedly reduced the extent of thymidine incorporation into the cells (Table I). Treatment with BVDU alone (69.5 mg kg-1) or 5-FU alone (12.5 to I00mgkg-1), did not affect the growth of MOPC-315 tumour in vivo. If however, 5-FU treatment was combined with BVDU treatment, 5-FU at doses ranging from 25 to 100mg kg-1, caused a transient regression of MOPC-315 tumours and prolongation of survival time. The kinetics of tumour development are presented in Figures la, b and the rates of survival are shown in Figures 2a, b. The therapeutic index (TI) was 2.5 for mice treated with 5-FU alone (250 mg kg-1 MLD/100mgkg-1 MED) and 20.0 for mice treated with a combination of 5-FU plus BVDU (250mgkg-1 MLD/12.5mgkg-1 MED).
Our findings indicate that BVDU has a potentiating effect on the antitumour activity of 5-FU in mice bearing large progressively growing MOPC-315 tumours. These results are in agreement with previously reported data (Desgranges et al., 1986)  aMOPC-315 tumour cells were incubated for 1 h with the compound at 37°C and washed 3 times before culturing; tumour cells incubated in medium alone were used as controls; bTumour cells were cultured for 72h; [methyl-3H]thymidine (l uCi/culture) was added for the last 6h of incubation; 2 x 104 tumour cells/culture; cpm represent means (±s.e.) for 16 parallel samples; % of thymidine incorporation is expressed as function of the corresponding control.
on the synergistic antitumour activity of BVDU and 5-FU in DBA/2 mice inoculated with P388 leukaemia cells. BVDU alone does not affect MOPC-315 tumour cells either in vitro or in vivo. Since BVDU is readily converted in vivo to BVU (Desgranges et al., 1984) and since BVU is capable of inhibiting the degradation of 5-FU in vivo (Desgranges et al., 1986), one may postulate that the increased antitumour activity of combined BVDU and 5-FU therapy in the MOPC-315 model is due to a decrease in the degradation of 5-FU, and hence greater bio-availability of the compound.
Under the experimental conditions used (i.e. single doses of both BVDU and 5-FU), only a transient regression of MOPC-315 tumours was observed. It would seem imperative to examine whether a more intensive treatment regimen, i.e. higher doses of BVDU and/or repeated administrations of BVDU and 5-FU, may yield a more definitive prolonged or even definitive regression of MOPC-315 tumours. In any case, the combination of 5-FU and BVDU is an interesting lead that should be further pursued as a therapeutic modality in the treatment of cancer. Improvement in effectiveness of 5-FU therapy may be of importance in view of the doubts expressed (Drewinko & Yang, 1985) on the efficacy of therapy with this drug alone. 3 (----) inoculated, 5-FU 100 (mg kg-1) + BVDU 69.5 (mg kg 1). 4 (-----) inoculated, 5-FU 50 (mg kg-1). 5 ( --) inoculated, 5-FU 50 (mg kg-1) + BVDU 69.5 (mg kg 1).
We thank Abic, Israel for the generous supply of 5fluorouracil. This work was supported in part by an endowment bequeathed by Meir and Rebecca Heinik in memory of their son Joseph Heinrichson.